Fact Sheet 7
Induced Pluripotent Stem Cells (iPS cells)
Stem cell science is an extremely fast moving field of research with new breakthroughs being
reported almost daily. This swiftly changing landscape has seen many different stem cell types
and technologies capture popular imagination including embryonic stem cells (ES cells), adult
stem cells, cord blood stem cells and embryonic germ stem cells. Currently attracting a lot of
public attention are some recent breakthroughs in the areas of reprogramming and in particular
the discovery of a way to make a new cell type which has been named induced pluripotent stem
cells (iPS cells).
The term reprogramming is often used to refer to techniques developed by scientists to change
the developmental potential or fate of a cell. The objective of reprogramming is to take a defined
cell from the body (somatic cell), such as a skin cell, and convert it to more primitive stem cell
which would be capable of developing into another cell type such as a heart or blood cell.
Currently there are two different approaches to reprogramming being investigated by scientists
around the world: somatic cell nuclear transfer (SCNT) which is covered in the ASCC’s Fact
Sheet No.4; and the creation of iPS cells.
Both types of reprogramming are of great interest to scientists as they represent ways to
potentially create patient-specific cells to study particular diseases in the laboratory or even
provide replacement cells to treat a patient which would not be rejected by the immune system.
However, both types of reprogramming research are in the very early stages and are many years
away from a therapeutic use.
Induced Pluripotent Stem Cells
iPS cells are a type of pluripotent cell 1 artificially derived from a non-pluripotent cell, such as an
adult human skin cell. This is achieved by using retroviruses to insert four genes into the human
skin cells to reprogram them. Following insertion of the four genes, 4-5 weeks of culture in the
laboratory is required before rare iPS cells begin to appear. To date, only between one in 5000
to one in 10000 somatic cells converts to iPS cells. Little is currently understood what actually
occurs during this time however the process should become more efficient and better understood
as research progresses.
iPS cells were first produced in 2006 from adult mouse cells by Shinya Yamanaka and his team
at Kyoto University in Japan 2 . More recently, human iPS cells have been reported by several
groups from Japan and the United States 3, 4 , 5 .
Pluripotent—Ability of a single stem cell to give rise to all of the various cell types that make up the
Takahashi, K. and Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult
fibroblast cultures by defined factors. Cell 2006, Vol 126, pp663–676.
Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti
V, Stewart R, Slukvin II, Thomson JA. Induced pluripotent stem cell lines derived from human somatic
cells. Science, 2007, vol 318, pp1917-20.
Fact Sheet 7 – Page 1
iPS cells are believed to be similar to embryonic stem cells 6 (ES cells are considered the ‘gold
standard’ of pluripotent cells) in many respects but the full extent of their relationship to
embryonic stem cells is still being assessed. The iPS cells generated in the recent experiments
shared many characteristics of human ES cells but were not identical as the expression level of
approximately 1,200 genes was greater than five fold different when the two pluripotent cell types
Whilst an undeniable breakthrough in the field of reprogramming, the use of iPS cells in the clinic
is many years away - if it occurs at all - as several significant hurdles need to be overcome. A
downside of all the current ways to generate human iPS cells is the use of retroviruses to
genetically engineer the cells to achieve reprogramming. It is still unclear how genetically stable
or safe iPS cells will be for potential clinical use. Consideration of safety must also consider the
implication of the over-expression of specific reprogramming genes especially when several
approaches to date have relied on the over-expression of cancer causing genes.
Much of the current public interest and support surrounding iPS cells is due to the fact that
generation of iPS cells bypasses the need to use human oocytes or embryos, in contrast to other
methods of generating pluripotent stem cells.
Position of the Australian Stem Cell Centre
The successful generation of human iPS cells has led some to call for a ban on human ES cell
research and SCNT 7 . Although the generation of iPS cells avoid some of the ethics issues
associated with the use of human oocytes and embryos, issues associated with obtaining
informed consent and safety for therapeutic applications remain.
The Australian Stem Cell Centre believes it is too early to draw conclusions about which types of
cells – ES, SCNT, iPS or adult stem cells – will prove most useful for researchers and in the
clinic (refer to ASCC Fact Sheet No 2 for an overview of all the different types of stem cells). It is
also too early to know which approaches will work in which conditions 8 and would be extremely
premature and a serious mistake for any government or regulatory authority to conclude that
recent developments in iPS cell research averts the need for ongoing human ES cell research.
There remains overwhelming scientific justifications for proceeding with all forms of stem cell
research into the future 9 . Cell types made from human embryonic stem cells have been shown
to be genetically stable in many laboratories around the world and are about to be used in human
clinical trials to treat spinal cord injury in California 10 . Stability of human iPS cells and full ES cell
equivalence is yet to be demonstrated.
Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S.. Induction of
pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007, vol 131(5), pp861-
Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, Lerou PH, Lensch MW, Daley GQ.
Reprogramming of human somatic cells to pluripotency with defined factors. Nature, 2008, Vol451, No
Embryonic stem cells—Primitive (undifferentiated) cells derived from a 5-7 days preimplantation
embryo that have the potential to become a wide variety of specialised cell types.
Editorial. Proceed With Caution. Nature Biotechnology. Vol 23, pp 763.
Hyun, I et al. New Advances in iPS Cell Research Do Not Obviate the Need for Human Embryonic Stem
Cells, Cell Stem Cell, 2007, Vol 1, pp 367.
Fact Sheet 7 – Page 2
What is required is the continuation of well regulated research in Australia consistent with current
legislation governing the responsible use of human embryos and gametes in research 11 and
guidelines such as the National Statement on Ethical Conduct in Human Research (2007). In
addition, research involving iPS cells would also have to be performed in accordance with the
Gene Technology Act 2000 and overseen by the Office of the Gene Technology Regulator due to
the genetic modification that is required.
Current Known iPS Cell Research Funding Initiatives
The US National Institutes of Health on 13 December 2007 put out a new funding
announcement 12 for Human Pluripotent Stem Cell Research Using Non-Embryonic Sources
specifically aimed at research into reprogramming and iPS cells. The total funding available has
not been specified.
The new California Institute of Regenerative Medicine (CIRM) president has indicated that CIRM
has a strong interest in funding iPS and reprogramming research 13 , however at time of writing no
program has been announced.
Germany currently has extremely restrictive legislation with regard to research on human ES
cells. Under the German Stem Cell Act, derivation of human ES cells is prohibited and only stem
cell lines created before January 1st, 2002 may be imported for use in research. However,
Germany has pledged to invest more money in adult stem-cell research after the iPS
breakthroughs in Japan and the US. The country's research minister Annette Schavan has
announced that it will “double research funds for the technology for reprogramming adult cells
from €5 to €10 million a year, so that work can proceed quickly". 14 Germany has no special
legislation on the preparation and use of iPS cells.
This invention is recent and it is their opinion that special legislation is not really needed as adult
SC will be used for those experiments only. On the contrary Germany has now expanded its fund
for reprogramming research activities. Therefore the embryo protection act still defines and
protects the embryo and the Stem Cell Act still prohibits the work and establishment of human
ES cells with the exception of importing cells which had been established before Jan 1 2002 15 .
The Japanese Government has proposed to spend up to ¥10 billion over the next five years to
promote research on iPS cells. The proposal also includes the setting up of major iPS research
centre at Kyoto University 16 .
Prohibition of Human Cloning for Reproduction and the Regulation of Human Embryo Research
Amendment Act 2006 as found at http://www.comlaw.gov.au
Education and Research Minister Annette Schavan told the newsmagazine Focus http://www.dw-
Additional information on iPS research has been provided to the ASCC by the Stem Cell Network
North Rhine Westphalia, Germany’s leading stem cell group.
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Where is the iPS Cell Research Occurring?
At time of writing the groups involved in or known to be interested in getting involved in research
into iPS cells are:
Department Cell &
James Thomson, Developmental
University of Sir Ian Biology Max Planck
Wisconsin- Wilmut, Institute, Munster,
Madison, Madison, Rudolph Scottish Germany Shinya Yamanaka,
Wisconsin, USA Jaenisch, Centre for Department of Stem Cell Biology,
Whitehead Regenerative Institute for Frontier Medical
Institute for Medicine, Sciences, Kyoto University, Kyoto,
Harvard Medical South China Institute of Stem Cell
School and Harvard Biology and Regeneration Medicine
Stem Cell Institute, ran a training course in Dec 08 to
Boston, USA train 16 Chinese scientists in iPS
Fact Sheet 7 – Page 4